Marie Passet, Rathana Kim, Emmanuelle Clappier, Blood, 2025

B-cell acute lymphoblastic leukemia (B-ALL) is a rare malignancy in adults, with outcomes remaining poor, especially compared with children.

Over the past 2 decades, extensive whole-genome studies have identified numerous genetic alterations driving leukemia, leading to the recognition of >20 distinct subtypes that are closely associated with treatment response and prognosis.

In pediatric B-ALL, large correlation studies have made genetic classification a central component of risk-adapted treatment strategies.

Notably, genetic subtypes are unevenly distributed according to age, and the spectrum of genetic alterations and their prognostic relevance in adult B-ALL have been less extensively studied, with treatment primarily based on the presence or absence of BCR::ABL1 fusion.

This review provides an overview of genetic subtypes in adult B-ALL, including recent biological and clinical insights in well-established subtypes as well as data on newly recognized subtypes.

Their relevance for risk classification, disease monitoring, and therapeutic management, including in the context of B-cell-directed therapies, is discussed.

This review advocates for continuing efforts to further improve our understanding of the biology of adult B-ALL to establish the foundation of future precision medicine in B-ALL.

Voir la publication